LAUSR

Significance We have made a surprising discovery linking Delta/Notch signaling in subperineurial glia (SPG) to the regulation of nerve ensheathment and neurotransmitter release at the Drosophila neuromuscular junction (NMJ). SPG, the counterpart of the endothelial layer in the vertebrate blood–brain barrier, form the key cellular layer that is critical for axonal ensheathment and the blood–brain barrier in Drosophila. Our findings demonstrate that Delta/Notch signaling exerts a constitutive negative inhibition on JNK signaling in SPG, thereby limiting the expression of Mmp1, a matrix metalloproteinase. SPG-specific and temporally regulated knockdown of Delta leads to breakdown of barrier function and compromises neurotransmitter release at the NMJ. Our results provide a mechanistic insight into the biology of barrier function and glia–neuron interactions.